WO2007105179A1 - Solution cardioplégique - Google Patents

Solution cardioplégique Download PDF

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Publication number
WO2007105179A1
WO2007105179A1 PCT/IB2007/050878 IB2007050878W WO2007105179A1 WO 2007105179 A1 WO2007105179 A1 WO 2007105179A1 IB 2007050878 W IB2007050878 W IB 2007050878W WO 2007105179 A1 WO2007105179 A1 WO 2007105179A1
Authority
WO
WIPO (PCT)
Prior art keywords
cardioplegic solution
cardioplegic
cardiac
solution
xylitol
Prior art date
Application number
PCT/IB2007/050878
Other languages
English (en)
Inventor
Erich Gygax
Thierry Carrel
Hendrik Tevaearai
Original Assignee
Universitat Bern
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Universitat Bern filed Critical Universitat Bern
Priority to EP07735117A priority Critical patent/EP1996181A1/fr
Priority to US12/281,671 priority patent/US20110020475A1/en
Publication of WO2007105179A1 publication Critical patent/WO2007105179A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
    • A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
    • A61K31/245—Amino benzoic acid types, e.g. procaine, novocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Definitions

  • the invention relates to cardiac surgery. It more precisely concerns a cardioplegic solution which can be used during cardiac surgery.
  • Cardioplegia from a surgical point of view, is an induced cardiac arrest achieved by a solution perfused through the cardiac vessels, either in an antegrade way through the coronary arteries, or retrogradely through the coronary veins. From a physiologic point of view, it represents a possibility to reversibly arrest the heart. Finally, from a metabolic point of view, it protects the cardiac cells again the possible damages induced by the temporary absence of oxygenation.
  • solutions have been tried and are routinely used in cardiac surgery in the world. These are:
  • the inventors have surprisingly discovered that an improved cardioplegic solution can be obtained if it contains the following elements :
  • the solution is preferably buffered to pH 6.5.
  • the solution is advantageously buffered with 0.1 M sodium hydroxide to pH 6.5.
  • the solution according to the present invention provides in particular the following advantages :
  • the solution according to the present invention contribute to improve the overall results and in particular the early outcome of this type of surgery. 2.
  • the total volume of the solution according to the invention may be of only 100ml.
  • the solution according to the invention allows an extended effect of at least 60 minutes with one single injection. A repeated injection or a continuous perfusion is required with all other available cardioplegic solutions. Similarly to what was just described earlier, this advantage permits the reduction of the operative and ischemic times with the subsequent already mentioned benefit.
  • the solution according to the invention provides a higher myocardial protection as compared to other currently available solutions. Indeed, the inventors have found that the level of post-operative cardiac enzymes, in other words markers of cardiac cellular lesions, is reduced as compared to other cardioplegic solutions. Finally, the hearts return spontaneously much more frequently into a sinus rhythm at the end of the procedure.
  • the solution is prepared at room temperature , typically between 18 and 24 C.
  • the preparations are considered to be safely usable when kept at 4 C for a maximum period of 30 days.
  • the substances included in the solution are mixed together in non-labeled 50 ml ready-to-use syringes.
  • 160 mmol/1 of sodium and 53.2 mmol/1 of citrate may be used. Sterilization may be carried out during 20 minutes at 120 0 C .
  • CPB CPB is initiated and conducted at a 100% flow rate.
  • the ascending aorta is cross-clamped and the cardioplegic solution is injected into the aortic root.
  • the heart immediately stops and the cardiac procedure can start immediately thereafter. Exceptionally, the content of a third 50 ml syringe needs to be injected, typically in patients with a higher BMI. Topic cooling is not excluded. At the end of the procedure, no hot shot is required before the aorta is declamped.
  • the cardioplegic solution according to the invention was tested in several patients. The inventors did not record any single adverse effect that could be related to this solution. As compared to cardioplegic solutions of the state of the art, the solution according to the invention appears very efficient in terms of time to total cardiac arrest (immediate) and protection. The post-operative recovery is accelerated.
  • the cardioplegic solution according to the invention may advantageously be used for coronary artery bypass procedures performed with a MECC (mini-ECC), a circuit designed to minimize the adverse effects of a standard cardiopulmonary bypass by reducing for example the priming volume (volume required to fill the system before it is connected to the patient) as well as the inflammatory reactions induced by the contact of blood with foreign materials (oxygenator, heat exchanger, tubings, filters, etc).
  • the cardioplegia is initiated by the initial administration of 100 ml of the cardioplegic solution according to the invention followed by the traditional 5 minutes perfusion with conventional blood cardioplegic mixture.
  • a single 100 ml cardioplegic injection is sufficient.

Abstract

La présente invention concerne une nouvelle solution cardioplégique destinée à arrêter et protéger le muscle cardiaque lors d'interventions chirurgicales. À base de sulphate de magnésium heptahydraté, de chlorure de potassium, de procaîne chlorhydrate et de xylitol, la solution cardioplégique selon l'invention offre plusieurs avantages notoires par rapport aux solutions classiques disponibles.
PCT/IB2007/050878 2006-03-15 2007-03-14 Solution cardioplégique WO2007105179A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP07735117A EP1996181A1 (fr) 2006-03-15 2007-03-14 Solution cardioplégique
US12/281,671 US20110020475A1 (en) 2006-03-15 2007-03-14 Cardioplegic solution

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IBPCT/IB2006/050815 2006-03-15
IB2006050815 2006-03-15

Publications (1)

Publication Number Publication Date
WO2007105179A1 true WO2007105179A1 (fr) 2007-09-20

Family

ID=38235426

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2007/050878 WO2007105179A1 (fr) 2006-03-15 2007-03-14 Solution cardioplégique

Country Status (4)

Country Link
US (1) US20110020475A1 (fr)
EP (1) EP1996181A1 (fr)
CN (1) CN101400345A (fr)
WO (1) WO2007105179A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010020904A2 (fr) * 2008-08-22 2010-02-25 Universität Bern Préparation cardioplégique

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103933540A (zh) * 2014-03-26 2014-07-23 王寿世 一种心脏停搏液
CN106659677A (zh) 2014-07-11 2017-05-10 有氧运动系统制药有限责任公司 通用心脏麻痹液(多种变型)
RU2635523C2 (ru) * 2016-04-29 2017-11-13 Общество С Ограниченной Ответственностью "Кардиосистемфарма" (Ооо "Ксф") Способ проведения кардиоплегии

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1986000812A1 (fr) * 1984-07-30 1986-02-13 Pharmacia Ab Composition medicamenteuse ou medicament sous forme de kit utilises pour la prevention et le traitement de degats causes a des cellules ischemiques, et sa preparation

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1986000812A1 (fr) * 1984-07-30 1986-02-13 Pharmacia Ab Composition medicamenteuse ou medicament sous forme de kit utilises pour la prevention et le traitement de degats causes a des cellules ischemiques, et sa preparation

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
HÖLSCHER B: "Reperfusion effects on the magnesium-procaine arrested rabbit heart", ARZNEIMITTEL FORSCHUNG. DRUG RESEARCH, ECV EDITIO CANTOR VERLAG, AULENDORF, DE, vol. 31, no. 11, 1981, pages 1881 - 1884, XP008081493, ISSN: 0004-4172 *
JYNGE P: "Protection of the ischemic myocardium: Cold chemical cardioplegia, coronary infusates and the importance of cellular calcium control", THORACIC AND CARDIOVASCULAR SURGEON, THIEME MED. PUB., NEW YORK, NY,, US, vol. 28, no. 5, 1980, pages 310 - 321, XP008081445, ISSN: 0171-6425 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010020904A2 (fr) * 2008-08-22 2010-02-25 Universität Bern Préparation cardioplégique
WO2010020904A3 (fr) * 2008-08-22 2010-07-22 Universität Bern Préparation cardioplégique
US20110183010A1 (en) * 2008-08-22 2011-07-28 Erich Gygax Cardioplegic preparation
US9763979B2 (en) 2008-08-22 2017-09-19 Universitat Bern Cardioplegic preparation

Also Published As

Publication number Publication date
US20110020475A1 (en) 2011-01-27
EP1996181A1 (fr) 2008-12-03
CN101400345A (zh) 2009-04-01

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